1. Field of the Invention
The present invention is broadly concerned with a new instrument and method useful in behavioral neuroscience and psychopharmacological research typically involving in vivo test subjects such as rats or mice. More particularly, the invention pertains to a combined actometric and ergometric locomotor activity-measuring device referred to as a xe2x80x9cforce plate actometer,xe2x80x9d which can simultaneously perform functions now requiring three or more separate instruments. The force plate actometer is operable to determine on a real time basis variations in location and/or magnitude of the force exerted by a test subject on the device. With this information, it is possible to determine and quantify a number of different movements or sequences of movements of a test subject, such as tremor, rearing, velocity of locomotion, tendency to turn right or left and stereotypies.
2. Description of the Prior Art
The fields of behavioral neuroscience, psychopharmacology, toxicology and physiology often make use of in vivo test animals, most commonly rats and mice. Such animals are treated with experimental drugs or subjected to experimental procedures, whereupon one or more locomotor activities of the animals are observed and quantified. This type of research is often carried out in studies of genetics of Alzheimer""s disease, behavioral genetics involving gene knockout mice bearing on a large number of central nervous system diseases, animal models of addiction, compounds to combat drug abuse, anti-schizophrenia drug discovery, research on the genetic determinants of ethanol sensitivity, Parkinson""s disease research, animal models of mental retardation, self-injurious behavior, attention deficit disorder, learning disorders, neurotoxicology and virtually all central nervous system drug discovery research.
A number of different devices are used by researchers in these fields to measure animal locomotor activity. For example, one popular instrument is a photobeam actometer which detects animal activity via a grid of IR beams. Movement of the animal within the device causes some of these beams to be broken, thus revealing the animal""s position in the X, Y plane. These devices also include an optional vertical Z axis activity sensor to monitor rearing or jumping activity. In these types of devices, the spatial resolution is fixed by the distance between photoemitter-detector pairs, typically 2.5 cm, giving a spatial resolution on the order of about 2.5 cm.
However, photobeam actometers are inherently limited in that they cannot simultaneously detect and quantify a variety of other motions of a test animal. Therefore, other types of activity-measuring devices have been developed, including single force transducer ergometric activity chambers (ergometric in this context meaning the measurement of energy expenditure), and video-based tracking systems for subjects where a video camera is mounted above the chamber and records the animal""s movement. However, none of these devices is well suited for quantifying rat stereotypies, and neither can quantify drug-induced or lesion-induced tremor. Rotometers have also been developed which are designed to measure the number of rotations of an animal. These devices include a harness fitted to the animal with the harness being attached to a rotary counter. This eliminates the need for a human observer to count the number of turns. However, the presence of the harness serves as an animal constraint, making it difficult to know the effect of the harness on animal activity. Furthermore, these rotometers are incapable of simultaneously measuring other locomotor activities.
There is accordingly a real and unsatisfied need in the art for improved animal testing devices which can simultaneously and in real time detect and quantify a variety of different possible locomotor activities, thereby eliminating the need for extra testing equipment and the respective tests each individual instrument requires.
The present invention overcomes the problems outlined above, and provides an in vivo force plate actometer testing device in the form of a plate presenting an upper surface adapted to support a test subject, with at least three (and preferably four) transducers operably coupled with the plate at fixed relative locations. The transducers are each operable to sense a parameter resulting from movement of a test subject on the plate, and to generate an output correlated with the sensed parameter. A processor (typically a PC) is coupled with the transducers to receive the outputs, with the processor operable to perform calculations and recordings using the outputs to determine at least one attribute of the movement of the test subject. Preferably, the transducers are selected from the group consisting of force and pressure transducers, with the former being most preferred. The preferred force transducers must be capable of measuring both static and dynamic forces.
With this force plate actometer, it is possible to determine on a real time basis the variation in location and/or magnitude of the force exerted by the subject on the plate. With this knowledge, it is possible, through use of appropriate processor software, to determine and/or quantify a variety of attributes of the movement of the test subject. Thus, attributes selected from the group consisting of the position of the subject on the plate, distance traveled by the subject over a defined period of time, the angle and direction of rotation of movement, a spatial statistic of the movement of the subject, stereotypies, tremor and wall rearing can be accurately measured. Furthermore, this can be accomplished without the need for human or video camera monitoring of the test.
In preferred forms, the overall force plate actometer includes a rigidly mounted enclosure for confining the test subject to a predefined region of the force plate. This enclosure is spaced slightly above the force plate but is supported to prevent displacement thereof by a test animal. The enclosure may be any desired shape, but usually square or circular in plan enclosures are used.
As indicated, the force plate actometer is capable of performing real time calculations. The results of these real time calculations are stored and are used in post-test period calculations to develop further locomotor and/or motion information about the test animal. During the course of the tests, the processor repeatedly performs an initial set of calculations, with the interval between successive calculations being up to about 1 second, and more preferably from about 0.01-0.1 seconds.
The force plate actometer can thus be used to perform a variety of animal study tests. Besides those mentioned previously, the device can quantify the motor concomitants of drug-induced seizures; can count and quantify the intensity of vertical jumps (as in the xe2x80x9cpoppingxe2x80x9d behavior induced in mice by NMDA antagonists such as MK-801) and the spatial location of such jumps; can measure total energy expenditure due to movement during a test period; when fitted with proper attachments, it can be used to develop automated y mazes, t mazes or radial mazes for mouse or rat studies of learning (discrimination learning, discrimination reversal learning, spatial learning, and working memory); be adapted to acoustic startle paradigms (such as the prepulse inhibition paradigm, thought to yield information about some of the neurological mechanisms of schizophrenia and other psychopathologies); and can be incorporated into the floor of an operant chamber to provide descriptions of animal behavior both during bouts of lever pressing and when lever pressing is not occurring.